The Molecular Biology of Epidermal Growth Factor Receptor and Its Role in Human Breast Cancer

[摘要] This thesis deals with a number of aspects of Epidermal Growth Factor Receptor (EGF-R) molecular biology and also EGF-R's involvement in breast cancer. The current literature on the biology of breast cancer and on the structure of both the EGF-R gene and protein are reviewed, as are the ways in which advances in technology have contributed to our knowledge in these areas. The link between EGF-R structure and function is emphasised and this leads into a discussion on EGF-R signal transduction. EGF-R is a 160 K.D. polypeptide which has intrinsic tyrosine kinase activity. The cellular substrates of the kinase are largely unknown but many of those that have been identified have been shown to be important structural and regulatory proteins. EGF-R also has autophosphorylation ability i.e. EGF-R phosphorylates itself as well as exogenous substrates. This is a very important process and is believed to have a regulatory function, possibly mediated by structural features of the receptor and is discussed in some depth. In order to more clearly understand the ways in which EGF-R may be involved in human carcinogenesis, and to put the problem in context, a review of the very large and complicated area of cancer biology is included. In addition, the specific case of breast cancer molecular biology is examined in some detail. EGF-R has been shown to be an important regulator of growth in both normal and cancerous cells. In breast cancer, EGF-R has been reported to be an index of poor prognosis, both in relation to disease free interval and total survival. The current literature concerning EGF-R's role in human breast cancer development is often conflicting; Points reviewed in this thesis include the autocrine theory of growth factor involvement in growth regulation, EGF-R and breast cancer cell proliferation, and EGF-R as a potential therapuetic target.

[发布机构] University:University of Glasgow

[关键词] Biochemistry